Novel Bromo and methoxy substituted Schiff base complexes of Mn(II), Fe(III), and Cr(III) for anticancer, antimicrobial, docking, and ADMET studies.

In this study, four new Mn(II), Fe(III), and Cr(III) complexes with two Schiff base ligands namely, 4-bromo-2-[(E)-{[4-(2-hydroxyethyl)phenyl]imino}methyl]phenol (HL1) and 2-[(E)-{[4-(2-hydroxyethyl)phenyl]imino}methyl]-4-methoxy phenol (HL2) have been synthesized and characterized. Different analytical and spectral methods have been used to characterize the ligands and their complexes. General formulas of [M(L)Cl2(H2O)2] for FeL1, CrL1 and CrL2, and [M(L)Cl(H2O)3] for MnL2 were proposed. HOMO and LUMO energies, as well as the electrical characteristics, have been calculated using DFT/B3LYP calculations with Gaussian 09 program. The optimized lowest energy configurations of the complexes are proven. The disc diffusion technique was used to test the pharmacological activities' antibacterial efficacy against diverse bacterial and fungus species. The MTT technique was used to assess the in vitro cytotoxicity of the ligands and their metal complexes on the Hep-G2 human liver carcinoma cell line and the MCF-7 human breast cancer cell line. All compounds displayed better activity compared to the free ligands. MnL2 complex showed predominant activity when compared to the other complexes with an IC50 value of 2.6 ± 0.11 µg/ml against Hep-G2, and against MCF-7 the IC50 value was 3.0 ± 0.2 µg/ml which is less than the standard drug cisplatin (4.0 µg/ml). UV-vis electronic spectrum and gel electrophoresis techniques have been used to investigate the compounds' affinity to bind and cleavage CT-DNA. The interaction's binding constants, or Kb, have been identified, and it was discovered that the new complexes' binding affinities are in the order of FeL1 > MnL2 > CrL2 > CrL1, and the binding mechanism has been suggested. To assess the kind of binding and binding affinity of the investigated drugs with human DNA, a molecular docking study was carried out (PDB:1bna). The acquired results supported the intercalation binding mechanism proposed in the experimental part and revealed that complexes may be inserted into the DNA molecule to stop DNA replication. According to ADMET data, the synthesized compounds have a high bioavailability profile and their physicochemical and pharmacological features remained within Lipinski's RO5 predicted limitations.

Aspirin-Based Organoiron Dendrimers as Promising Anti-Inflammatory, Anticancer, and Antimicrobial Drugs.

Designing nanocarriers with actions directed at a specific organ or tissue is a very promising strategy since it can significantly reduce the toxicity of a bioactive drug. In this study, an organometallic dendrimer was used to synthesize a biocompatible drug delivery system by attaching aspirin to the periphery of the dendrimer. Our goal is to enhance the bioavailability and anticancer activity of aspirin and reduce its toxicity through successive generations of organoiron dendrimers. The biological activity of aspirin-based dendrimer complexes was evaluated. The result of antimicrobial activity of the synthesized dendrimers also demonstrated an increase in their antimicrobial activity with increased generation of the dendrimers for most types of microorganisms. This study reveals for the first time that organoiron dendrimers linked with aspirin exhibit an excellent Gram-negative activity comparable to the reference drug Gentamicin. All synthesized dendrimers were tested for their anticancer activity against breast cancer cell lines (MCF-7), hepatocellular cell lines (Hep-G2), and a non-cancer cell line, Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, Doxorubicin. Compounds G3-D9-Asp and G4-D12-Asp exhibited noticeable activity against both cell lines, both of which were more effective than aspirin itself. In addition, the in vivo anti-inflammatory activity and histopathology of swollen paws showed that the designed aspirin-based dendrimers displayed significant anti-inflammatory activity; however, G2-D6-Asp showed the best anti-inflammatory activity, which was more potent than the reference drug aspirin during the same period. Moreover, the coupling of aspirin to the periphery of organoiron dendrimers showed a significant reduction in the toxicity of aspirin on the stomach.

Development of Ferromagnetic Materials Containing Co2P, Fe2P Phases from Organometallic Dendrimers Precursors.

The development of synthesis methods to access advanced materials, such as magnetic materials that combine multimetallic phosphide phases, remains a worthy research challenge. The most widely used strategies for the synthesis of magnetic transition metal phosphides (TMPs) are organometallic approaches. In this study, Fe-containing homometallic dendrimers and Fe/Co-containing heterometallic dendrimers were used to synthesize magnetic materials containing multimetallic phosphide phases. The crystalline nature of the nearly aggregated particles was indicated for both designed magnetic samples. In contrast to heterometallic samples, homometallic samples showed dendritic effects on their magnetic properties. Specifically, saturation magnetization (Ms) and coercivity (Hc) decrease as dendritic generation increases. Incorporating cobalt into the homometallic dendrimers to prepare the heterometallic dendrimers markedly increases the magnetic properties of the magnetic materials from 60 to 75 emu/g. Ferromagnetism in homometallic and heterometallic particles shows different responses to temperature changes. For example, heterometallic samples were less sensitive to temperature changes due to the presence of Co2P in contrast to the homometallic ones, which show an abrupt change in their slopes at a temperature close to 209 K, which appears to be related to the Fe2P ratios. This study presents dendrimers as a new type of precursor for the assembly of magnetic materials containing a mixture of iron- and cobalt-phosphides phases with tunable magnetism, and provides an opportunity to understand magnetism in such materials.

Pharmacological Evaluation of Novel Organoiron Dendrimers as Antimicrobial and Anti-Inflammatory Agents.

The synthesis of a novel and attractive class of nonsteroidal anti-inflammatory and antimicrobial organoiron dendrimers attached to the well-known drug ibuprofen is achieved. The structures of these dendrimers are established by spectroscopic and analytical techniques. The antimicrobial activity of these dendrimers is investigated and tested against five human pathogenic Gram-positive and Gram-negative bacteria, and minimum inhibitory concentrations are reported. Some of these synthesized dendrimers exhibit higher inhibitory activity against methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and Staphylococcus warneri compare to the reference drugs. As well, the in vitro and in vivo anti-inflammatory activities of these dendrimers are evaluated. The results of in vivo anti-inflammatory activity and histopathology of inflamed paws show that all dendrimers display considerable anti-inflammatory activity; however, second-generation dendrimer (G2-D6) shows the best anti-inflammatory activity, which is more potent than the commercial drug ibuprofen at the same tested dose. Results of the toxicity study reveal that G2-D6 is the safest drug on biological tissues.

Design of Organoiron Dendrimers Containing Paracetamol for Enhanced Antibacterial Efficacy.

Paracetamol (acetaminophen) is a common painkiller and antipyretic drug used globally. Attachment of paracetamol to a series of organoiron dendrimers was successfully synthesized. The aim of this study is to combine the benefits of the presence of these redox-active organoiron dendrimers, their antimicrobial activities against some human pathogenic Gram-positive, and the therapeutic characteristics of paracetamol. The antimicrobial activity of these dendrimers was investigated and tested with a minimum inhibitory concentration and this has been reported. Some of these newly synthesized dendrimers exhibited the highest inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), and Staphylococcus warneri compared to reference drugs. The results of this study indicate that the antimicrobial efficacy of the dendrimers is dependent on the size of the redox-active organoiron dendrimer and its terminal functionalities. The best result has been recorded for the fourth-generation dendrimer 11, which attached to 48 paracetamol end groups and has 90 units composed of the η6-aryl-η5-cyclopentadienyliron (II) complex. This dendrimer presented inhibition of 50% of the growth (IC50) of 0.52 µM for MRSA, 1.02 µM for VRE, and 0.73 µM for Staphylococcus warneri. The structures of the dendrimers were characterized by elemental analysis, Fourier transform infrared (FT-IR), nuclear magnetic resonance (1H-NMR), and 13C-NMR spectroscopic techniques. In addition, all synthesized dendrimers displayed good thermal stability in the range of 300-350 °C following the degradation of the cationic iron moieties which occurred around 200 °C.

Anti-inflammatory drug approach: Synthesis and biological evaluation of novel pyrazolo[3,4-d]pyrimidine compounds.

In this study, the acid chlorides of pyrazolo[3,4-d]pyrimidine compounds were prepared and reacted with a number of nucleophiles. The novel compounds were experimentally tested via enzyme assay and they showed cyclooxygenase-2 inhibition activity in the middle micro molar range (4b had a COX-1 IC50 of 26 µM and a COX-2 IC50 of 34 µM, 3b had a COX-1 IC50 of 19 µM and a COX-2 IC50 of 31 µM, 3a had a COX-2 IC50 of 42 µM). These compounds were analyzed via docking and were predicted to interact with some of the COX-2 key residues. Our best hit, 4d (COX-1 IC50 of 28 µM, COX-2 IC50 of 23 µM), appears to adopt similar binding modes to the standard COX-2 inhibitor, celecoxib, proposing room for possible selectivity. Additionally, the resultant novel compounds were tested in several in vivo assays. Four compounds 3a (COX-2 IC50 of 42 µM), 3d, 4d and 4f were notable for their anti-inflammatory activity that was comparable to that of the clinically available COX-2 inhibitor celecoxib. Interestingly, they showed greater potency than the famous non-steroidal anti-inflammatory drug, Diclofenac sodium. In summary, these novel pyrazolo[3,4-d]pyrimidine analogues showed interesting anti-inflammatory activity and could act as a starting point for future drugs.

Advances in Light-Emitting Dendrimers.

The design of dendrimers with various chromophores has attracted significant attention in light of the dual effect of the luminescence of the chromophores and the morphology of the synthesized dendrimers. Recent developments in this field stem from their wide potential applications, including organic light-emitting diodes, photonic switches and upconversion lasers, as well as sensors and electronic devices. The focus of this comprehensive review is on the design and properties of various classes of light-harvesting dendrimeric materials.